The invention relates in general to biocompatible medical structures, and in particular to a process to assure at least long-term dermal contact biocompatibility for three-dimensional objects formed from solid freeform fabrication techniques such as stereolithography. In one application the process is capable of producing a long-term dermal contact hearing aid shell structure custom made by stereolithography.
Conventional biocompatible and bioabsorbable materials have been proposed previously for long-term dermal contact applications, such as hearing aids. Generally, biocompatible materials exhibit non-toxic characteristics and do not adversely react with biological matter. Biocompatible testing is often done by placing a material in contact with living cells of an animal for extended periods of time in order to verify that no adverse reaction occurs. Bioabsorbable materials, on the other hand, while also exhibiting non-toxic characteristics, are capable of breaking down into small, non-toxic segments, which can be metabolized or eliminated from the body without harm. Both biocompatible and bioabsorbable materials lack the presence of significant amounts of cytotoxins, that is, substances or particulates that can produce a toxic effect to cells. Identifying specific cytotoxins in a specific material can prove problematic; however, cytotoxicity testing can readily be conducted to essentially determine whether or not a significant level of cytotoxins are present in a particular material. Until recently, the development of biocompatible materials for use in solid freeform fabrication techniques has been limited.
Generally, cytotoxins are constituent species of matter that, when in physical contact with cells, produce a toxic effect such as an allergic reaction. When present in sufficient quantity in an object, cytotoxins render the object unacceptable for biocompatible applications such as long-term dermal contact. Nearly all objects contain some quantity of cytotoxins, however the conventional wisdom to achieve biocompatibility is to start with a material that is inherently non-toxic, i.e. one that contains a de-minimus amount of cytotoxins. For example, several acrylate and methacrylate-type polymers have previously been suggested for a wide variety of applications involving some degree of biocompatibility because many such materials contain a de-minimus amount of cytotoxins. U.S. Pat. No. 5,763,503 to Cowperthwaite, et al. discloses a pourable methacrylate-capped urethane monomer/reactive diluent composition for use in pouring into a mold to form a hearing aid shell structure. Thus, it is generally taught that in order to produce a biocompatible object, one must start by selecting a material that is inherently non-toxic, i.e., one that contains a de-minimus amount of cytotoxins.
Recently, several new technologies have been developed for the rapid creation of models, prototypes, and parts for limited run manufacturing. These new technologies can generally be described as Solid Freeform Fabrication techniques, herein referred to as xe2x80x9cSFFxe2x80x9d. Some SFF techniques include stereolithography, laminated object manufacturing, selective phase area deposition, multi-phase jet solidification, ballistic particle manufacturing, fused deposition modeling, particle deposition, laser sintering, and the like. Generally in SFF techniques, complex parts are produced from a modeling material in an additive fashion as opposed to traditional fabrication techniques, which are generally subtractive in nature. For example, in traditional fabrication techniques material is removed by machining operations or shaped in a die or mold to near net shape and then trimmed. In contrast, additive fabrication techniques incrementally add portions of a build material to targeted locations, layer by layer, in order to build a complex part. SFF technologies typically utilize a computer graphic representation of a part and a supply of a building material to fabricate the part in successive layers. A wide variety of building materials have been proposed in various SFF techniques; however, they are typically applied in the form of a powder, liquid, gas, paste, or gel. SFF technologies have many advantages over conventional manufacturing methods. For instance, SFF technologies dramatically shorten the time to develop prototype parts and can produce limited numbers of parts in rapid manufacturing processes. They also eliminate the need for complex tooling and machining associated with conventional manufacturing methods, including the need to create molds for custom applications. In addition, customized objects can be directly produced from computer graphic data. However, the use of SFF techniques to produce biocompatible objects has been limited.
It has been envisioned that prosthetic implants could be constructed directly from SFF techniques such as stereolithography. Such biocompatible applications are believed possible because polymerizable acrylates have previously been shown to be biocompatible, and it is assumed that objects formed from these materials in stereolithographic processes will therefore be biocompatible. For example, International Patent Application WO 95/07509 envisions the direct production of implants from a stereolithographic process, however, only the use of a stereolithographic object as an intermediate mold to create biocompatible prostheses is disclosed. This illustrates the recognized inability to directly produce biocompatible objects directly from a stereolithographic process utilizing materials believed to be biocompatible. Thus, there is a need to develop a process in which biocompatible objects can be produced directly by SFF techniques.
Most attempts to achieve biocompatible or bioabsorbable objects formed by SFF techniques have focused primarily on build material formulation. For example, a bioabsorbable stereolithographic resin is disclosed in U.S. Pat. No. 5,674,921 to Regula et al., which comprises a radiation curable, urethane acrylate and a photoinitator. However, it is significant to note that the samples disclosed were completely cured by flood curing with a UV light source, and not by a selectively applying a concentrated beam of UV energy as is done in stereolithography techniques. Furthermore, the formulations were not designed to be biocompatible, but rather bioabsorbable, that is, intended to break down into small non-toxic segments within a biological environment, instead of simply remaining stable and inert within the biological environment.
What appears to be under-appreciated in the prior art is that where the SFF build process produces parts that are typically toxic, additional post processing methods may be deployed to render them non-toxic. In addition, due to the inherently non-homogeneous nature of most SFF build processes, it is theorized that cytotoxins are typically retained within structures formed by such processes. This has been shown to be the case in stereolithography, and even when a part is homogeneously formed by stereolithography, it may still contain cytotoxins. These cytotoxins can undesirably react with biological matter in certain applications, particularly those requiring long-term dermal contact. It is the creation and/or retention of cytotoxins in these structures that presently prevents their use in biocompatible applications.
Generally, in most SFF techniques, structures are formed in a layer by layer manner by solidifying successive layers of a build material that are inherently non-homogeneous. For example, in stereolithography a tightly focused beam of energy, typically in the ultraviolet radiation band, is scanned across a layer of a liquid photopolymer resin to selectively solidify the resin to form a structure. In order to solidify each built up layer of the structure, the focused beam of energy must be driven back and forth across its surface. This build process, or hatching, often does not form a homogeneously cured layer because the focused energy only locally activates the photoinitiator in the resin. There is a wide variety of hatching techniques used in SFF techniques that can produce varying degrees of non-homogeneity within the structures produced. A representative example of the variety of build techniques available are disclosed in, for example, U.S. Pat. No. 5,855,718 to Nguyen et al. At one extreme is the investment casting build technique discussed in U.S. Pat. No. 5,482,659 to Sauerhoefer, in which a generally hollow structure is formed that requires the removal of a substantial amount of un-solidified liquid resin material. Generally the structures formed by most SFF processes such as stereolithography are not homogeneous. In stereolithography, after selective solidification, some locations of the polymers are highly cross-linked while in other locations they are partially cross-linked, or not cured at all. It is believed that uncured resin and/or partially cured resin are likely to contain toxic species.
The non-homogeneous aspect or non-uniform cure that results from some stereolithography hatching patterns is often desirable in many applications. For example, many hatching techniques are used to reduce cracking or distortion of the structure while it is being formed, even though cytotoxins are likely to be left behind in the structure. Some hatching techniques are used to increase build speed by reducing the amount of scanning of the laser, thereby leaving even a greater quantity of cytotoxins behind. In most of these non-biological applications, a simple UV postcure and wash is all that is needed to prepare the structure for use. Ultrasonic washing has been used, for example, with acetone as disclosed in U.S. Pat. No. 5,639,413 to Crivello, and with alcohol as disclosed in U.S. Pat. No. 5,482,650 to Sauerhoefer. Although such techniques are useful for washing and removing un-solidified resin material, they are not sufficient by themselves to detoxify structures for biocompatibility applications. Thus, objects cleansed by these techniques typically remain toxic even after cleaning.
It is believed the non-homogeneous cure that occurs when scanning a laser beam across a layer of polymerizable build material in a stereolithographic process becomes most problematic when trying to achieve biocompatibility for stereolithographic structures. It is believed the cytotoxins present in the formed object may be any combination of monomers, oligomers, photoinitiators, free radicals, polyols, photogenerated acid, stabilizers, and the like, that are originally present in the resin or generated during the cure of the resin. It is believed that portions of these cytotoxins are sufficiently entrapped such that they are not removed by simple washing operations and therefore remain in the structure. Thus, regardless if a fully cured resin formulation is believed to be biocompatible, the structures formed from the resin in a stereolithographic apparatus may still contain cytotoxins and as such may not be acceptable for use in biocompatible applications.
For example, a liquid acrylate photopolymer resin for use in stereolithography equipment sold by the name STERECOL Y-C 9300R has been proposed to produce low toxicity objects. The resin was designed for use in stereolithography equipment using a solid state or Argon laser to form three-dimensional objects. This resin was formerly manufactured and sold by Avecia Limited, of Manchester, England. Currently this resin is manufactured by Vantico, Inc. of Los Angeles, Calif., and is sold by 3D Systems, Inc. of Valencia, Calif. Preliminary objects made with this resin according to the recommended processing parameters provided by Avecia Limited failed to pass cytotoxicity tests for biocombatibility. It is theorized that cytotoxins were either established in or already present during the layer by layer forming process and their existence is believed most likely to be a result of insufficient cross-linking, incomplete cure, or continued reactivity after formation.
Thus, there is a need to nullify the cytotoxins within an SFF structure in order to render the structure biocompatible for at least long-term dermal contact. Thus, there is a need to develop a process beyond simple washing in order to assure such structures are detoxified regardless of the build technique or hatching style used during their formation. These and other difficulties of the prior art have been overcome according to the present invention.
The present invention provides its benefits across a broad spectrum of medical devices, implants, and structures. While the description which follows hereinafter is meant to be representative of a number of such applications, it is not exhaustive. As will be understood, the basic methods and products taught herein can be readily adapted to many uses. It is intended that this specification and the claims appended hereto be accorded a breadth in keeping with the scope and spirit of the invention being disclosed despite what might appear to be limiting language imposed by the requirements of referring to the specific examples disclosed.
It is one aspect of the present invention to provide a process for detoxifying a three-dimensional object formed by a SFF technique by nullifying the cytotoxins that exist within the object after the layer by layer build process.
It is another aspect of the present invention to provide a process to assure at least long-term dermal contact biocompatibility for three-dimensional objects formed from SFF build materials such as liquid polymerizable resins used in stereolithography.
It is yet another aspect of the present invention to directly produce custom made biocompatible medical devices or structures by SFF techniques including stereolithography.
It is a feature of the present invention to detoxify a three-dimensional object formed by a SFF technique by entrapping at least some of the cytotoxins within the object.
It is another feature of the present invention to detoxify a three-dimensional object formed by a SFF technique by extracting at least some of the cytotoxins out of the object.
It is yet another feature of the present invention to detoxify a three-dimensional object formed by a SFF technique by decomposing at least some of the cytotoxins into a non-toxic state within the object.
It is yet another feature of the present invention to detoxify a three-dimensional object formed by a SFF technique by advancing the state of cure of the object.
It is yet another feature of the present invention to incorporate a simple and repeatable post-processing step to detoxify three-dimensional objects formed from SFF build materials including liquid polymerizable resins used in stereolithography.
It is still yet another feature of the present invention to develop a SFF build style that nullifies some of the cytotoxins within the three-dimensional object by advancing the state of cure of the object during object formation.
It is an advantage of the present invention to directly create biocompatible medical structures without first creating a mold in which to form the structure.
It is another advantage of the present invention to directly produce biocompatible medical structures from data descriptive of the structures that can be generated by computer models and used in any SFF technique.
It is yet another advantage of the present invention detoxification process to make available the benefits of solid freeform fabrication techniques to applications requiring some level of biocompatibility.
These and other aspects, features, and advantages are achieved/attained in the method and apparatus of the present invention.